tbuckley/cabot-search huggingface dataset:
Results from plasmaMATCH trial cohort E: A phase II trial of olaparib and ceralasertib in patients with triple-negative advanced breast cancer (CRUK/15/010).
Authors: Alistair E. Ring, Laura Moretti, Angelica Afshari-Mehr, Andrew M. Wardley, Lucy Kilburn, Bora Gurel, Iain R. MacPherson, Richard D. Baird, Sue Martin, Alex Pearson, Rebecca Roylance, Matthew Winter, Kathryn Dunne, Ellen Copson, Tamas Hickish, Peter Stephens, Russell J. Burcombe, Katrina Randle, Judith Bliss, Nicholas C. Turner
Journal: Journal of Clinical Oncology (2022)

1024 Background: The plasmaMATCH trial was an open label platform trial, consisting of circulating tumour DNA (ctDNA) testing in ̃1000 patients with advanced breast cancer (ABC) linked to parallel treatment cohorts with therapies matched to mutations identified in ctDNA. Cohorts A-D have already reported (Turner N et al, Lancet Oncol 2020). Cohort E recruited patients with triple negative breast cancer (TNBC) without a targetable mutation identified at ctDNA screening, treating with olaparib (PARP inhibitor) plus ceralasertib (ATR inhibitor). Methods: Patients with TNBC who had received 1 or 2 lines of chemotherapy for advanced disease or relapsed within 12 months of (neo)adjuvant chemotherapy were eligible. Treatment was olaparib 300mg b.i.d continuously and ceralasertib 160mg qd on days 1–7 on a 28 day cycle, until disease progression. The primary endpoint was confirmed objective response rate by RECIST v1.1. Secondary endpoints included clinical benefit rate, progression-free survival (PFS) and safety. Biomarker analysis included response according to BRCA and somatic DNA repair gene status and ATM loss. Using a two-stage design with a target response rate of 25%, unacceptable response rate of 10%, alpha=2% and power=90%, ≥13 responses out of 69 evaluable stage 2 patients were required to infer efficacy (5/37 stage 1). Results: Between 17/09/18 and 5/10/20 75 patients enrolled in Cohort E of whom 70 were evaluable for response. The median age was 55.6 years. 42 (56%) patients had 1 and 13 (17.3%) had 2 prior line(s) of chemotherapy for metastatic disease. Efficacy is shown in Table. The most common grade ≥3 adverse events were: hypertension 12 (17%) and anaemia 9 (13%). Dose reductions and interruptions occurred in 19 (26.4%) and 34 (47.2%) patients respectively. Conclusions: The response rate to olaparib and ceralasertib did not meet pre-specified criteria for efficacy in the overall evaluable population. Responses were observed in patients without germline or somatic BRCA1/2 mutations. Translational analyses are underway to identify potential biomarkers of response in this population and will be presented at the meeting. Clinical trial information: ISRCTN16945804. [Table: see text]
MEDB-37. Chemotherapy response prediction by molecular risk factors in metastatic childhood medulloblastoma
Authors: Denise Obrecht, Michael Ludwig Bockmayr, Brigitte Bison, Stefan M Pfister, Dominik Sturm, Felix Sahm, David T W Jones, Martin Sill, Katja von Hoff, Martin Benesch, Nicolas U Gerber, André von Bueren, Carsten Friedrich, Torsten Pietsch, Ulrich Schüller, Martin Mynarek, Stefan Rutkowski
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Childhood metastatic medulloblastoma (MB) frequently receive postoperative chemotherapy (CT) before craniospinal irradiation. Some MB show stable (SD) or progressive disease (PD) upon CT. Identification of biomarkers for non-response might allow therapy-modifications. METHODS: Patients registered to the German HIT-MED database (2001–2019) were eligible if they were 4-21 years old at diagnosis of a M2/M3-metastasized MB, received therapy in analogy to the MET-HIT2000-AB4 protocol, had centrally reviewed response assessment after 2 cycles HIT-SKK-CT and DNA-methylation analysis was available. DNA-methylation-based tumor classification and whole chromosomal (WC) losses/gains were derived from DNA-methylation arrays. RESULTS: 51/163 (31.3%) patients (median age: 9.8±4.4 years, median follow-up: 6.2±4.0 years) presented SD/PD during/after HIT-SKK-CT and were classified as non-responder. Response to CT had high predictive value for PFS/OS (5-year PFS responder: 67.9±4.8 %, non-responder: 26.1±6.6%, p&amp;lt;0.01 / 5-year OS responder: 80.0±4.2%, non-responder: 45.9±8.0%, p&amp;lt;0.01). Patients with nonWNT/nonSHH-MB subtype II (response: 7/13), subtype III (response: 6/19) and/or MYC-amplification (n=27, overlap subtype II/III: n=11/8, response: 14/27) were less likely to respond, while all 6 of WNT, 8/9 SHH-TP53-wildtype and 1/1 SHH-TP53-mutant responded (Mann-Whitney-U-test p=0.04). Further, ≥2 WC losses/gains of chromosome 7/8/11 was associated with superior response (n=29/32, others: n=83/131, Mann-Whitney-U-test p&amp;lt;0.01). We identified a very-high-risk-cohort (any two criteria of: &amp;lt;2 WC losses/gains of chromosome 7/8/11, MYC-amplification, MB subtype II, III, V, or VIII, n=94), and a standard-risk-cohort (WNT or any ≥2 WC losses/gains of chromosome 7/8/11, n=37) with 40 vs. 8 % non-response and 44±5/60±5 vs. 79±7/87±6% 5-year PFS/OS (p&amp;lt;0.01/p&amp;lt;0.01), respectively. Non-response in n=32 non-VHR/non-SR-patients was 32% with a 5-years PFS/OS of 60±10/77±8%. CONCLUSION: Molecular information can be helpful to predict response to chemotherapy. Upon validation, this may contribute to improve treatment stratification in metastatic MB.
The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases: A multicenter cohort study.
Authors: Roger Olofsson Bagge, Carl Jacob Holmberg, Tina J. Hieken, Jonathan S. Zager, Georgina V. Long, Alexander Christopher Jonathan Van Akkooi, Giorgos C Karakousis, Lalit Pallan, John T. Vetto, David E. Gyorki, Paolo Antonio Ascierto, Reinhard Dummer, Jane Yuet Ching Hui, Jacob Schachter, Hildur Helgadottir, Hidde Kroon, Luke Daniel Rothermel, Matteo S. Carlino, Kristy Kummerow Broman, Lars Ny
Journal: Journal of Clinical Oncology (2022)

9569 Background: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The aim of this study was to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international high‐volume melanoma centers. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c and N3c) and without distant disease (M0). Patients were treated with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). We assessed response rates, progression-free survival (PFS), melanoma-specific survival (MSS) and overall survival (OS). Results: A total of 287 patients from 21 institutions in 8 countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. Monotherapy with a PD-1 or CTLA-4 inhibitor was given in 233 (81%) and 23 (8%) patients respectively, while 31 (11%) received both in combination. Overall response rate was 56%, complete response (CR) rate 36% and progressive disease (PD) rate 32%. Median PFS was 10 months (95% CI 7.4-12.6 months) with a 1-, 2- and 5-year PFS rate of 48%, 33% and 18% respectively. Median MSS was not reached, and the 1-, 2- and 5-year MSS rates were 95%, 83% and 71% respectively. Conclusions: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the optimal role for systemic immunotherapy in the context of multimodality therapy including locoregional treatments such as surgery, intralesional therapy, and regional therapies.
Change in telomere length and cardiovascular risk in testicular cancer survivors.
Authors: Ellen L.D. Volders, Coby Meijer, Lotte S. Steeneken, Sjoukje Lubberts, Nynke Zwart, Arie M. van Roon, Joop D. Lefrandt, Igle Jan de Jong, Marco Demaria, Janine Nuver, Jourik A. Gietema
Journal: Journal of Clinical Oncology (2022)

12079 Background: Testicular cancer (TC) survivors cured with chemotherapy (CT) are prone to develop cardiovascular events, as part of an early aging phenotype. Telomere shortening could be a mechanism contributing to these events and their risk factors. Methods: In a prospectively followed cohort of patients with disseminated TC who received cisplatin containing CT (Lubberts et al., Eur J Cancer 2016), mean absolute leukocyte telomere length (TL) was measured using qPCR before and one year after start of cisplatin containing CT. Cardiovascular risk factors, including development of the metabolic syndrome (according to the NCEP ATP III definition) and hypogonadism (LH &gt;10 U/L or testosterone &lt; 10 nmol/L or use of testosterone suppletion), were assessed before and up to 5 years after CT. Shortening of TL was defined as a decrease of &gt;33% after one year compared to baseline; short TL was defined as &lt;5 kilobase (kb) pair (=P25). Data are presented as median (range). For comparisons, a Mann-Whitney U or Chi-Square test was applied. Results: 55 out of 73 patients of the initial cohort were evaluable for this analysis. CT regimens consisted of 3xBEP (n=41), 4x BEP (n=11), 4xEP (n=3). At baseline, patients with a BMI &gt; 30 kg/m2 (n=12) had a shorter TL (4.9 (2.2-13.4) vs. 6.3 kb (3.1-12.9), p=.045); there was no difference in age. For the whole group, TL did not change one year after CT compared to baseline (5.7 (2.2-13.4) vs. 5.8 kb (1.6-19.2), p=.335). Patients with TL shortening after 1 year (n=7) showed a significant increase in diastolic blood pressure (p=.007) and triglycerides (p=.003), compared to those with unchanged TL (table). TL shortening after 1 year or short TL at baseline (n=7+11) are not significant predictors for newly developed metabolic syndrome (25 vs. 21%; p=.777), nor hypogonadism (38 vs. 17%; p=.120) after 5 years, compared to the others. Conclusions: A small subset of TC patients treated with cisplatin containing CT showed shortening of TL 1 year after treatment. This shortening is associated with a rise in diastolic blood pressure and triglycerides. Short or shortening of telomeres are not predictive for development of the metabolic syndrome or hypogonadism. [Table: see text]
V-FAST master trial: Preliminary results of treatment with CPX-351 plus midostaurin in adults with newly diagnosed <i>FLT3</i>-mutated acute myeloid leukemia.
Authors: James K. McCloskey, Vinod A. Pullarkat, Gabriel N. Mannis, Tara L. Lin, Stephen Anthony Strickland, Amir Tahmasb Fathi, Harry Paul Erba, Stefan Faderl, Divya Chakravarthy, Yana Lutska, Vijayalakshmi Chandrasekaran, Ronald Cheung, Mark J. Levis
Journal: Journal of Clinical Oncology (2022)

7043 Background: CPX-351 (US: Vyxeos; Europe: Vyxeos liposomal), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved for newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes in patients aged ≥1 year in the US and in adults in Europe. In a phase 3 study in older adults with newly diagnosed, high-risk/secondary AML, CPX-351 significantly improved overall survival and remission rates versus conventional 7+3, with a comparable safety profile. Preclinical data suggest CPX-351 may have synergistic activity with targeted agents, including the FLT3 inhibitor midostaurin (MID). Herein, we report preliminary results for the cohort of adults treated with CPX-351 + MID in the V-FAST (Vyxeos – First Phase Assessment with Targeted Agents) trial. Methods: V-FAST is an open-label, multicenter, multiarm, nonrandomized, phase 1b master trial (NCT04075747) to evaluate the safety and preliminary efficacy of CPX-351 combined with targeted agents (midostaurin, venetoclax, enasidenib). Eligible adults in the CPX-351 + MID cohort were aged 18 to 75 years, had newly diagnosed AML with a FLT3 internal tandem duplication (ITD) or tyrosine kinase domain (TKD) mutation, were fit for intensive chemotherapy, and had an ECOG performance status of 0 to 2. The dose-exploration phase (3+3 design) determined a recommended phase 2 dose of CPX-351 100 units/m 2 (daunorubicin 44 mg/m 2 + cytarabine 100 mg/m 2 ) on Days 1, 3, and 5 + MID 50 mg BID on Days 8 to 21. There were no dose-limiting toxicities, and additional patients were enrolled in the expansion phase at this dose. Results: A total of 23 patients received CPX-351 + MID and had sufficient data to be included in the analysis (cutoff date: 1/20/2022). Patient baseline characteristics are shown in the Table. Treatment-emergent adverse events (TEAEs) in ≥40% of patients included febrile neutropenia (78%), nausea (65%), increased alanine aminotransferase (57%), leukopenia (57%), thrombocytopenia (57%), headache (43%), and hyponatremia (43%). All patients experienced a grade 3/4 TEAE, primarily hematologic events. Nonhematologic grade 3/4 TEAEs in ≥2 patients included pneumonia (17%), lung infection (13%), and hyperglycemia (9%). There were no grade 5 TEAEs and no deaths on or before Day 60. Complete remission was achieved by 18/22 (82%) evaluable patients after the first induction cycle. Conclusions: Preliminary results from the V-FAST trial suggest CPX-351 + MID is feasible, with a manageable safety profile and promising remission rates in adults with newly diagnosed AML who have a FLT3 mutation. Clinical trial information: NCT04075747. [Table: see text]
Symptom profile of head and neck patients initiating care in a survivorship clinic.
Authors: Katherine Ramsey Gilmore, Kate A. Hutcheson, Patricia Hansberry Chapman, Weiqi Bi, Ryan Goepfert, Kristen B Pytynia, Maria Alma Rodriguez
Journal: Journal of Clinical Oncology (2022)

e24047 Background: After treatment, and at a time point of low risk of relapse, cancer patients at our institution transition to Survivorship Clinics (SC) that focus on wellness, late effects management, and psychosocial functioning in additional to cancer screening. We describe the self-reported symptoms of Head and Neck (HNC) survivors at the time of transition to SC, and the level to which these symptoms interfered with their function. Methods: Survivors reporting to their first in person SC appointment were assessed using the MD Anderson Symptom Inventory Head and Neck (MDASI–HN). This validated patient-reported outcome (PRO) instrument consists of 28 questions grouped into three subscales (core symptoms, disease specific symptoms, and interference items). Symptom severity is measured using a 0 to 10 scale (0 = not present, 10 = as bad as can be imagined). Descriptive statistics were used to characterize the sample. Percent of patients reporting moderate to severe symptoms (&gt; = 4) are also noted. Results: This sub-analysis consisted of 377 patients seen for their initial transition visit to the survivorship clinic. Patients were mostly male (83%) and Caucasian (89%), with an average age of 63.8 years, and on average 41.5 months from diagnosis. Most common cancers were oropharynx (49%), oral cavity (33.7%), and larynx/hypopharynx (12.5%), nasopharynx (4.5%). Average symptom reports are presented in table. In rank order of prevalence (4% to 31% of patients), the top reported moderate to severe symptoms included dry mouth, swallowing/chewing, mucus, remembering, distress, and shortness of breath associated with moderated to severe interference in general activity in 8% of patients. Conclusions: HNC survivors report multiple persistent symptoms of moderate to high severity in a significant number, most commonly mouth dryness and swallowing and chewing difficulty. PROs can identify patients with high symptom burden, and lead in interventions to support the patients at their SC visit.[Table: see text]
Racial and Ethnic Disparities in Dementia Care
Authors: Norma B. Coe, Courtney Lee
Journal: JAMA Network Open (2022)

Pei-Jung Lin, PhD; Yingying Zhu, PhD; Natalia Olchanski, PhD; Joshua T. Cohen, PhD; Peter J. Neumann, ScD; Jessica D. Faul, PhD; Howard M. Fillit, MD; Karen M. Freund, MD, MPH
From patient generated data to precision medicine: An example of a patient-centered application in oncology.
Authors: Chantal N.L. Beutter, Uwe Marc Martens, Christian Fegeler
Journal: Journal of Clinical Oncology (2022)

e13559 Background: To practice precision medicine, the inclusion of patients in therapy is becoming increasingly important. Terms such as ‘patient empowerment’ (PE), ‘patient reported outcome’, and ‘patient generated data’ (PGD) are becoming quite present in current research. In order to implement PE consistently and integrate PGD in therapy, it is necessary to provide patients with specific tools. Methods: In order to develop such a corresponding system, challenges for implementation were identified as well as the current state of PGD in oncology. The aim was to design a system suitable for everyday use that allows the measurement of individual effects like quality of life (QoL) directly at the patient. Based on the positive experience of a previous developed questionnaire tool (EQU) to support physician-patient communication and the findings of the methodology a new patient-centered system was conceptualized with an automated data collection using sensor systems. A decisive factor was to support patients in self-management between treatment periods. This solution was then discussed extensively with stakeholders in order to identify and prioritize functionality and therefore incorporate specific user needs of oncological patients. Results: A great acceptance and need for tools to support patients especially between appointments was identified. In order to enable the recognition of individual characteristics, a continuous survey is essential. Based thereon an application called Lion-App for longitudinal QoL assessment in oncology was developed. A user-centered development aligns the app with the needs of the patients while HL7 FHIR provides the framework for an interoperable exchange. To reduce the burden of continuous interaction, sensors are used for data collection. With an interpretation of this data in the context of QoL, patients are able to visualize their personal course to gain an even better understanding of their disease. With the possibility to perform self-management between appointments, patients are lifted to another level of empowerment. In addition, the gained knowledge may then be used to focus on the effects of the disease in the next appointment and thus take a self-determined role in treatment. First evaluations of the app have been started. Conclusions: There are many ways to use PGD in the manner of precision medicine. The main factor is to create awareness among patients, collect data in an exchangeable way and involve end users early into development. A great opportunity to reduce user interactions and therefore enable long-term usage is the integration of sensor technologies. As a secondary use, algorithms can be extended via the expanded data base to become even more individualized to the patient. Thus, in the long run, such a system may help to further strengthen the cooperation between patient and physician and thus to enable a personalized, QoL-based treatment in oncology.
Prototype precision oncology learning ecosystem: Norwegian precision cancer medicine implementation initiative.
Authors: Kjetil Tasken, Hege Russnes, Aslaug Helland, Eline Aas, Line Bjørge, Egil Støre Blix, Espen Enerly, Gro Live Fagereng, Åsmund Flobak, Bjornar Gilje, Bjorn T. Gjertsen, Tormod Kyrre Guren, Jutta Heix, Eivind Hovig, Randi Hovland, Per Eystein Lonning, Per Magnus Maehle, Hilde Loge Nilsen, Steinar Osterbo Thoresen, Sigbjørn Smeland
Journal: Journal of Clinical Oncology (2022)

e13634 Background: Norway, a country with a publicly funded health care system, was in 2018-19 lagging behind with respect to implementation of precision cancer medicine (PCM). Methods: Our approach mid-2019 was very simple and set out three aims: i) To establish access to advanced molecular diagnostics to allow identification and stratification of cancer patients into clinical trials; ii) To increase the volume of clinical trials with a PCM approach to gain experience and build competence; and iii) In parallel work for implementation of PCM into standard of care. Results: In a trans-disciplinary project we worked along four lines: i) Gathered support to have oncologists, hematologists, pathologists and cancer researchers join a nation-wide, bottom-up initiative with a few common priorities; ii) Liaised with executives and regulators in regional health care systems, The Ministry of Health and other public stakeholders and charities to have the top-down approaches meet the bottom-up initiative; iii) Aligned with industry to explore the possibility of a public-private partnership and iv) Coordinated with other PCM initiatives internationally. Over the past two years we have thus built and raised funding for: a) The InPreD-Norway national infrastructure delivering precision cancer diagnostics for patient identification and stratification into clinical trials (publicly reimbursed) and operating the national molecular tumor board; b) the IMPRESS-Norway national researcher-initiated PCM intervention trial (https://impressnorway.com), which opened for inclusion Q2 2021 and runs at all hospitals that treat cancer patients (18 hospitals). The trial is modelled on and coordinated with the Dutch DRUP trial and aligned with similar trials in the Nordic countries; c) the INSIGHT/INCLUDE projects for research on control cohorts, use of real world evidence (RWE), health economics and reimbursement models, and ethics, legal aspects and governance; and d) the CONNECT public-private partnership (https://www.connectnorway.org) for PCM implementation with 29 partners (14 pharma &amp; biotech companies, 9 public partners and 4 NGOs) for interaction with InPreD and IMPRESS initiatives and providing a forum that includes regulators and payors for policy discussions of reimbursement models and regulatory framework. Conclusions: Our experience could serve as a model for building a functioning ecosystem for implementation of PCM. Unique aspects include the nation-wide initiative, the population effect of the diagnostics to be offered and the integration of a public-private partnership.
Identifying men affected by changes in PSA screening in the COVID-19 pandemic
Authors: E.J. Bass, M. Bertonelli Tanaka, M.J. Connor, U. Walters, D. Eldred-Evans, P. Sarkar, F. Hosking-Jervis, H. Bhola-Stewart, E. Pegers, L. Powell, D. Leelamany, K. Wong, S. Ahmad, H. Tam, S. Gordon, D. Hrouda, S. Mccracken, M. Winkler, H.U. Ahmed
Journal: European Urology (2022)